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1.
Int J Mol Sci ; 25(7)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38612545

RESUMEN

HIV-1 capsid protein (CA) is the molecular target of the recently FDA-approved long acting injectable (LAI) drug lenacapavir (GS-6207). The quick emergence of CA mutations resistant to GS-6207 necessitates the design and synthesis of novel sub-chemotypes. We have conducted the structure-based design of two new sub-chemotypes combining the scaffold of GS-6207 and the N-terminal cap of PF74 analogs, the other important CA-targeting chemotype. The design was validated via induced-fit molecular docking. More importantly, we have worked out a general synthetic route to allow the modular synthesis of novel GS-6207 subtypes. Significantly, the desired stereochemistry of the skeleton C2 was confirmed via an X-ray crystal structure of the key synthetic intermediate 22a. Although the newly synthesized analogs did not show significant potency, our efforts herein will facilitate the future design and synthesis of novel subtypes with improved potency.


Asunto(s)
Fármacos Anti-VIH , VIH-1 , Proteínas de la Cápside/genética , VIH-1/genética , Simulación del Acoplamiento Molecular , Fármacos Anti-VIH/farmacología , Mutación
2.
Nat Commun ; 15(1): 3128, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605096

RESUMEN

One of the strategies towards an effective HIV-1 vaccine is to elicit broadly neutralizing antibody responses that target the high HIV-1 Env diversity. Here, we present an HIV-1 vaccine candidate that consists of cobalt porphyrin-phospholipid (CoPoP) liposomes decorated with repaired and stabilized clade C HIV-1 Env trimers in a prefusion conformation. These particles exhibit high HIV-1 Env trimer decoration, serum stability and bind broadly neutralizing antibodies. Three sequential immunizations of female rabbits with CoPoP liposomes displaying a different clade C HIV-1 gp140 trimer at each dosing generate high HIV-1 Env-specific antibody responses. Additionally, serum neutralization is detectable against 18 of 20 multiclade tier 2 HIV-1 strains. Furthermore, the peak antibody titers induced by CoPoP liposomes can be recalled by subsequent heterologous immunization with Ad26-encoded membrane-bound stabilized Env antigens. Hence, a CoPoP liposome-based HIV-1 vaccine that can generate cross-clade neutralizing antibody immunity could potentially be a component of an efficacious HIV-1 vaccine.


Asunto(s)
Vacunas contra el SIDA , Infecciones por VIH , VIH-1 , Vacunas , Animales , Conejos , Femenino , Liposomas , Anticuerpos Neutralizantes , Fosfolípidos , Anticuerpos Anti-VIH , Inmunización , Productos del Gen env del Virus de la Inmunodeficiencia Humana
3.
Sci Rep ; 14(1): 8473, 2024 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605149

RESUMEN

Nearly half of the deaths among hospitalized human immuno deficiency virus-infected patients in the highly active antiretroviral therapy era have been attributed to liver disease. This may range from an asymptomatic mild increase of liver enzymes to cirrhosis and liver failure. Different works of literature elucidated both retroviral infection and the adverse effects of highly active antiretroviral therapy as a cause of hepatotoxicity. Individual adaptations to medications and environmental exposures, shaped by cultural norms and genetic predispositions, could potentially modulate the risk and progression of liver disease in this population. Therefore, this study aims to assess the predictors of severe hepatotoxicity in retroviral-infected adults receiving highly active antiretroviral therapy regimens within the Ilubabor Zone, Southwest Ethiopia. A facility-based cross-sectional study was conducted among adult retroviral-infected patients in five selected anti-retro virus therapy clinics from May1 to July 30/2022. A systematic sampling technique was used to select 457 study participants and Binary logistic regression statistical data analysis was used, P value < 0.05 was considered statistically significant. The prevalence of severe hepatotoxicity was 21.44% in the study population. CD+4 count < 200 cells/mm3 (AOR = 2.19, 95% CI 1.04-5.22, P = 0.01), human immunodeficiency virus co-infection with tuberculosis (AOR = 2.82, 95% CI 1.01-8.29, P = 0.03) and human immuno deficiency virus co-infection with hepatitis-B/hepatitis C virus (AOR = 5.02, 95% CI 1.82-16.41) were predictors of severe hepatotoxicity. The magnitude of severe hepatotoxicity was high among adult retroviral-infected patients on highly active anti-retroviral drug regimens. Co-infection of human immuno deficiency virus with hepatitis B virus or hepatitis C virus, tuberculosis and CD4+T-cell count below 200 cells/mm3 were predictors of severe hepatotoxicity. Therefore, HIV patients on highly active antiretroviral therapy require close attention and regular monitoring of their liver function.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Coinfección , Enfermedades del Sistema Digestivo , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Infecciones por VIH , Hepatitis C , Hepatopatías , Tuberculosis , Adulto , Humanos , Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Etiopía/epidemiología , Estudios Transversales , Hepatitis C/tratamiento farmacológico , VIH , Hepatopatías/etiología , Tuberculosis/tratamiento farmacológico , Hepacivirus , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Enfermedades del Sistema Digestivo/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Recuento de Linfocito CD4
4.
BMC Infect Dis ; 24(1): 390, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605325

RESUMEN

BACKGROUND: The world is moving towards the third target of the Joint United Nations Programme on HIV/AIDS to ensure most people receiving antiretroviral therapy (ART) are virologically suppressed. Little is known about viral suppression at an undetectable level and the risk of viral rebound phenomenon in sub-Saharan Africa which covers 67% of the global HIV burden.This study aimed to investigate the proportion of viral suppression at an undetectable level and the risk of viral rebound among people living with HIV receiving ART in northern Tanzania. METHODOLOGY: A hospital based-retrospective study recruited people living with HIV who were on ART for at least two years at Kibong'oto Infectious Disease Hospital and Mawenzi Regional Referral Hospital in Kilimanjaro Region, Tanzania. Participants' two-year plasma HIV were captured at months 6, 12, and 24 of ART. Undetectable viral load was defined by plasma HIV of viral load (VL) less than 20copies/ml and viral rebound (VR) was considered to anyone having VL of more than 50 copies/ml after having history of undetectable level of the VL less than 20copies/ml. A multivariable log-binomial generalized linear model was used to determine factors for undetectable VL and viral VR. RESULTS: Among 416 PLHIV recruited, 226 (54.3%) were female. The mean (standard deviation) age was 43.7 (13.3) years. The overall proportion of undetectable VL was 68% (95% CI: 63.3-72.3) and 40.0% had viral rebound (95% CI: 34.7-45.6). Participants who had at least 3 clinic visits were 1.3 times more likely to have undetectable VL compared to those who had 1 to 2 clinic visits in a year (p = 0.029). Similarly, participants with many clinical visits ( > = 3 visits) per year were less likely to have VR compared to those with fewer visits ( = 2 visits) [adjusted relative risk (aRR) = 0.64; 95% CI: 0.44-0.93]. CONCLUSION: Participants who had fewer clinic visits per year(ART refills) were less likely to achieve viral suppression and more likely to experience viral rebound. Enhanced health education and close follow-up of PLHIV on antiretroviral therapy are crucial to reinforce adherence and maintain an undetectable viral load.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Fármacos Anti-VIH , Infecciones por VIH , Humanos , Femenino , Adulto , Masculino , Estudios Retrospectivos , Terapia Antirretroviral Altamente Activa , Tanzanía/epidemiología , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Carga Viral , Fármacos Anti-VIH/uso terapéutico
5.
Elife ; 132024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38619110

RESUMEN

A productive HIV-1 infection in humans is often established by transmission and propagation of a single transmitted/founder (T/F) virus, which then evolves into a complex mixture of variants during the lifetime of infection. An effective HIV-1 vaccine should elicit broad immune responses in order to block the entry of diverse T/F viruses. Currently, no such vaccine exists. An in-depth study of escape variants emerging under host immune pressure during very early stages of infection might provide insights into such a HIV-1 vaccine design. Here, in a rare longitudinal study involving HIV-1 infected individuals just days after infection in the absence of antiretroviral therapy, we discovered a remarkable genetic shift that resulted in near complete disappearance of the original T/F virus and appearance of a variant with H173Y mutation in the variable V2 domain of the HIV-1 envelope protein. This coincided with the disappearance of the first wave of strictly H173-specific antibodies and emergence of a second wave of Y173-specific antibodies with increased breadth. Structural analyses indicated conformational dynamism of the envelope protein which likely allowed selection of escape variants with a conformational switch in the V2 domain from an α-helix (H173) to a ß-strand (Y173) and induction of broadly reactive antibody responses. This differential breadth due to a single mutational change was also recapitulated in a mouse model. Rationally designed combinatorial libraries containing 54 conformational variants of V2 domain around position 173 further demonstrated increased breadth of antibody responses elicited to diverse HIV-1 envelope proteins. These results offer new insights into designing broadly effective HIV-1 vaccines.


Asunto(s)
Vacunas contra el SIDA , Dermatitis , VIH-1 , Animales , Ratones , Humanos , VIH-1/genética , Formación de Anticuerpos , Estudios Longitudinales , Vacunas contra el SIDA/genética , Anticuerpos , Antígenos Virales
7.
Sci Rep ; 14(1): 8700, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622191

RESUMEN

HIV infection has been a global public health threat and overall reported ~ 40 million deaths. Acquired immunodeficiency syndrome (AIDS) is attributed to the retroviruses (HIV-1/2), disseminated through various body fluids. The temporal progression of AIDS is in context to the rate of HIV-1 infection, which is twice as protracted in HIV-2 transmission. Q-PCR is the only available method that requires a well-developed lab infrastructure and trained personnel. Micro-PCR, a portable Q-PCR device, was developed by Bigtec Labs, Bangalore, India. It is simple, accurate, fast, and operationalised in remote places where diagnostic services are inaccessible in developing countries. This novel micro-PCR determines HIV-1 and HIV-2 viral load using a TruePrep™ extractor device for RNA isolation. Five ml blood samples were collected at the blood collection centre at AIIMS, New Delhi, India. Samples were screened for serology, and a comparison of HIV-1/2 RNA was done between qPCR and micro-PCR in the samples. The micro-PCR assay of HIV-RNA has compared well with those from real-time PCR (r = 0.99, i < 0.002). Micro-PCR has good inter and intra-assay reproducibility over a wide dynamic range (1.0 × 102-1.0 × 108 IU/ml). The linear dynamic range was 102-108 IU/ml. The clinical and analytical specificity of the assay was comparable, i.e., 100%. Intra-assay and inter-assay coefficients of variation ranged from 1.17% to 3.15% and from 0.02% to 0.46%, respectively. Moreover, due to the robust, simple, and empirical method, the Probit analysis has also been done for qPCR LODs to avoid uncertainties in target recoveries. The micro-PCR is reliable, accurate, and reproducible for early detection of HIV-1 and HIV-2 viral loads simultaneously. Thus, it can easily be used in the field and in remote places where quantification of both HIV-1/2 is not reachable.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , VIH-1/genética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , ARN Viral/análisis , India , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , VIH-2/genética , Carga Viral/métodos
8.
BMC Pregnancy Childbirth ; 24(1): 278, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622544

RESUMEN

BACKGROUND: In 2015, Togo introduced the "test-and-treat" strategy for the prevention of mother-to-child transmission (PMTCT) of HIV. Pediatric HIV infection remains a public health problem in Togo, with a mother-to-child transmission (MTCT) rate of 3.6% in 2020. This study aimed to estimate cases of HIV seroconversion during pregnancy and to identify pregnant women at high risk of transmitting HIV to their children in Lomé, Togo. METHODS: A descriptive cross-sectional study was carried out from 18 March to 22 May 2022 among women who had given birth in five maternity units providing PMTCT services in Lomé. Umbilical cord blood samples were taken from the maternal side by midwives after delivery. HIV serology was performed in the laboratory using the Alere™ HIV Combo SET and First Response HIV 1-2. Card Test version 2.0. A sample was considered positive if both tests were positive. The HIV-1 viral load in HIV-1-positive samples was measured using Cobas/Roche 4800 equipment. Information on the women was extracted from maternal antenatal records and antenatal consultation registers. RESULTS: A total of 3148 umbilical cord blood samples (median maternal age: 28 years (interquartile range [24-32]) were collected. Among them, 99.3% (3145/3148) had presented for at least one antenatal clinic visit before giving birth, and 78.7% (2456/3122) had presented for at least four visits. One hundred and twenty-one (121) cord samples were HIV-1 positive, representing a seroprevalence of 3.8% (95% CI = [3.2-4.6]). Among them, 67.8% (82/121) were known HIV-positive before the current pregnancy, 29.7 (36/121) were diagnosed as HIV-positive at the antenatal visits and 2.5% (3/121) were diagnosed as HIV-positive in the delivery room. Of the HIV-positive women, 85.9% (104/121) were on ARV treatment before delivery. The viral load was < 1000 copies/ml in 97.5% (118/121) cases. CONCLUSION: This study explored the virologic and epidemiological aspects of HIV among pregnant women in Togo. The results show significant viral suppression at delivery in women ART. Surveillance based on umbilical cord blood specimen screening is an interesting approach for monitoring the effectiveness of PMTCT programmes.


Asunto(s)
Infecciones por VIH , Seropositividad para VIH , VIH-1 , Complicaciones Infecciosas del Embarazo , Embarazo , Femenino , Humanos , Adulto , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/prevención & control , Mujeres Embarazadas , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Togo/epidemiología , Estudios Transversales , Estudios Seroepidemiológicos
9.
S Afr Fam Pract (2004) ; 66(1): e1-e8, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38572873

RESUMEN

BACKGROUND:  The study explored and described the meaning attached to the lived experiences of women living with human immunodeficiency virus (HIV) in the rural context of Zimbabwe. Stigma and discrimination negatively impact one's ability to perform the expected social roles, the quality of life, and the efforts to prevent the spread of HIV and acquired immunodeficiency syndrome (AIDS) and reduce HIV-related mortality. Thus, the study aims to understand the meaning attached to the lived experiences of HIV-positive women living in rural areas or villages of Matabeleland South province in Zimbabwe. METHODS:  The study used a qualitative, descriptive, and exploratory design. Four focus group discussions were conducted with 24 HIV-positive rural women living in Matabeleland South province, Zimbabwe. An Interpretative Phenomenological Analysis (IPA) was adopted to explore and describe the meaning attached to the lived experiences of women living with HIV. RESULTS:  Two interconnected themes were identified in the analysis with their sub-themes. These were: (1) struggle for social belonging, with subthemes - loss of social belonging and reduced access to community-based empowerment opportunities and (2) struggle for maintaining the quality of life with subthemes - lack of need-based community healthcare and food insecurity. CONCLUSION:  Being a woman living with HIV in rural Zimbabwe means a perpetual struggle to maintain one's humanness and quality of life.Contribution: This study's results will support the efforts of the Zimbabwean government to improve the quality of life of HIV-positive women living in rural areas.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Seropositividad para VIH , Humanos , Femenino , Grupos Focales , Zimbabwe , Calidad de Vida
10.
Ann Intern Med ; 177(4): 518-526, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38588544

RESUMEN

Despite advances in treatment, HIV infection remains an important cause of morbidity and mortality, with more than 30 000 new cases diagnosed in the United States each year. There are several interventions traditionally used to prevent HIV transmission, but these vary in effectiveness and there are challenges to their implementation. In 2014, the Centers for Disease Control and Prevention published initial guidance on the use of antiretroviral pre-exposure prophylaxis (PrEP) to prevent transmission of HIV infection in persons at risk based on multiple studies that showed it to be highly efficacious in various populations. It was updated in 2021 to reflect new drug options. The U.S. Preventive Services Task Force also recently updated its recommendations for PrEP, which strongly support its use in persons at risk. Despite its well-established effectiveness, the implementation of PrEP in clinical practice has been variable, especially among populations underserved by the medical system and marginalized by society. Fewer than one third of persons in the United States who are eligible for PrEP currently receive it. Here, 2 physicians experienced in HIV PrEP debate how best to identify patients who might benefit from PrEP, how to decide what regimen to use, and how to monitor therapy.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Rondas de Enseñanza , Humanos , Estados Unidos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Antirretrovirales/uso terapéutico , Fármacos Anti-VIH/uso terapéutico
12.
J Int Med Res ; 52(4): 3000605241245011, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38606735

RESUMEN

Non-acquired immunodeficiency syndrome-defining cancers (NADCs) are malignancies in persons living with human immunodeficiency virus (PLWHIV) and are not primarily due to the host's immunodeficiency. There is renewed clinical interest in long-term morbidities in PLWHIV as well as malignancies that occur in this population. We herein describe a 36-year-old woman with a 2-year history of an anal wound and right breast mass. She had been diagnosed with HIV infection prior to the development of these lesions. Clinical and laboratory evaluations led to diagnoses of breast and anal cancers. Chemotherapy and antiretroviral therapy were begun, but the patient discontinued these treatments early and was lost to follow-up. NADCs will continue to be a major clinical issue as the global population ages. This presentation of two NADCs (breast and anal cancers) in a PLWHIV further highlights the burden of multiple malignancies on the depleted health of HIV-infected patients. Early identification and treatment of HIV upon patients' presentation to cancer care sites and screening for NADCs at HIV/AIDS care sites are recommended for improved outcomes.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Neoplasias del Ano , Carcinoma , Infecciones por VIH , Neoplasias , Femenino , Humanos , Adulto , Infecciones por VIH/epidemiología , Neoplasias/epidemiología , Síndrome de Inmunodeficiencia Adquirida/epidemiología , VIH , Neoplasias del Ano/complicaciones , Neoplasias del Ano/diagnóstico
13.
BMC Infect Dis ; 24(1): 396, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609839

RESUMEN

BACKGROUND: Tuberculosis (TB) and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) co-morbidity continues to be a serious worldwide health issue, particularly in Sub-Saharan Africa. Studies on the quality of life (QOL) of TB/HIV co-infected patients guide stakeholders on the delivery of patient-centred healthcare. This study evaluated QOL of TB/HIV co-infected individuals and its contributing factors. METHODS: We conducted a cross-sectional study among TB/HIV co-infected patients, receiving treatment at clinics in the Northern Region of Ghana. Simple random sampling technique was used to select 213 patients from 32 clinics. We gathered information on patients' QOL using the World Health Organization QOL-HIV BREF assessment tool. At a 5% level of significance, multiple logistic regression analyses were carried out to find correlates of QOL among the patients. RESULTS: The mean age of the patients was (38.99 ± 14.00) years with most, 33.3% (71/213) aged 30-39 years. Males constituted 54.9% (117/213). About 30.0% (64/213) of the patients reported a good QOL. Being employed (aOR = 5.23, 95% CI: 1.87 - 14.60), and adhering to treatment (aOR = 6.36, 95% CI: 1.51 - 26.65) were significantly associated with a good QOL. Being depressed (aOR = 0.02, 95% CI: 0.03 - 0.29), stigmatized (aOR = 0.31, 95% CI : 0.11 - 0.84), and not exercising (aOR = 0.28, 95% CI: 0.12 - 0.67) were negatively associated with a good QOL. CONCLUSION: Less than one-third of TB/HIV co-infected patients in the region have good QOL. To guarantee good QOL, modifiable predictors such as patients' physical activity and medication adherence should be targeted by the National AIDS and TB Control Programs.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Coinfección , Infecciones por VIH , Tuberculosis , Masculino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , VIH , Calidad de Vida , Ghana/epidemiología , Coinfección/epidemiología , Estudios Transversales , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Tuberculosis/complicaciones , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología
14.
Molecules ; 29(7)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38611779

RESUMEN

Drug discovery involves a crucial step of optimizing molecules with the desired structural groups. In the domain of computer-aided drug discovery, deep learning has emerged as a prominent technique in molecular modeling. Deep generative models, based on deep learning, play a crucial role in generating novel molecules when optimizing molecules. However, many existing molecular generative models have limitations as they solely process input information in a forward way. To overcome this limitation, we propose an improved generative model called BD-CycleGAN, which incorporates BiLSTM (bidirectional long short-term memory) and Mol-CycleGAN (molecular cycle generative adversarial network) to preserve the information of molecular input. To evaluate the proposed model, we assess its performance by analyzing the structural distribution and evaluation matrices of generated molecules in the process of structural transformation. The results demonstrate that the BD-CycleGAN model achieves a higher success rate and exhibits increased diversity in molecular generation. Furthermore, we demonstrate its application in molecular docking, where it successfully increases the docking score for the generated molecules. The proposed BD-CycleGAN architecture harnesses the power of deep learning to facilitate the generation of molecules with desired structural features, thus offering promising advancements in the field of drug discovery processes.


Asunto(s)
Fármacos Anti-VIH , Simulación del Acoplamiento Molecular , Descubrimiento de Drogas , Hidrolasas , Memoria a Largo Plazo
15.
Int J Mol Sci ; 25(7)2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38612471

RESUMEN

Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human immunodeficiency virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection from a fatal illness into a manageable chronic disorder. However, the presence of latent reservoirs, the multifaceted nature of HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict the efficacy of current cART targeting the distinct stages of the virus life cycle. Therefore, there is an unmet need for the discovery of new therapeutics that not only bypass the limitations of the current therapy but also protect the body's health at the same time. The main goal for complete HIV-1 eradication is purging latently infected cells from patients' bodies. A potential strategy called "lock-in and apoptosis" targets the budding phase of the life cycle of the virus and leads to susceptibility to apoptosis of HIV-1 infected cells for the elimination of HIV-1 reservoirs and, ultimately, for complete eradication. The current work intends to present the main advantages and disadvantages of United States Food and Drug Administration (FDA)-approved anti-HIV-1 drugs as well as plausible strategies for the design and development of more anti-HIV-1 compounds with better potency, favorable pharmacokinetic profiles, and improved safety issues.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , VIH-1 , Estados Unidos , Humanos , United States Food and Drug Administration , Apoptosis , División Celular
16.
Proc Natl Acad Sci U S A ; 121(15): e2316662121, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38557187

RESUMEN

Drug resistance in HIV type 1 (HIV-1) is a pervasive problem that affects the lives of millions of people worldwide. Although records of drug-resistant mutations (DRMs) have been extensively tabulated within public repositories, our understanding of the evolutionary kinetics of DRMs and how they evolve together remains limited. Epistasis, the interaction between a DRM and other residues in HIV-1 protein sequences, is key to the temporal evolution of drug resistance. We use a Potts sequence-covariation statistical-energy model of HIV-1 protein fitness under drug selection pressure, which captures epistatic interactions between all positions, combined with kinetic Monte-Carlo simulations of sequence evolutionary trajectories, to explore the acquisition of DRMs as they arise in an ensemble of drug-naive patient protein sequences. We follow the time course of 52 DRMs in the enzymes protease, RT, and integrase, the primary targets of antiretroviral therapy. The rates at which DRMs emerge are highly correlated with their observed acquisition rates reported in the literature when drug pressure is applied. This result highlights the central role of epistasis in determining the kinetics governing DRM emergence. Whereas rapidly acquired DRMs begin to accumulate as soon as drug pressure is applied, slowly acquired DRMs are contingent on accessory mutations that appear only after prolonged drug pressure. We provide a foundation for using computational methods to determine the temporal evolution of drug resistance using Potts statistical potentials, which can be used to gain mechanistic insights into drug resistance pathways in HIV-1 and other infectious agents.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , VIH-1/genética , Farmacorresistencia Viral/genética , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Mutación , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico
17.
BMC Infect Dis ; 24(1): 383, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589801

RESUMEN

BACKGROUND: Highly active antiretroviral therapy (HAART) has been able to improve the immune system function and survival of human immunodeficiency virus (HIV) patients. However, Patients coinfected with HIV and hepatitis B virus (HBV) are more likely to develop end-stage liver disease (ESLD) than those infected with HBV alone. Consequently, liver transplantation is often required for these patients. This study evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-HBV coinfected patients in China. METHODS: We conducted a retrospective analysis on all HIV-HBV coinfected patients that underwent OLT from April 1, 2019 to December 31, 2021 and their outcomes were compared to all HBV monoinfected patients undergoing OLT during the same period. Patient outcomes were determined, including cumulative survival, viral load, CD4 T-cell count and postoperative complications. RESULTS: The median follow-up of HIV recipients was 36 months after OLT (interquartile range 12-39 months). Almost all patients had stable CD4 T-cell count (> 200 copies/ul), undetectable HBV DNA levels, and undetectable HIV RNA load during follow-up. The 1-, 2-, and 3-year posttransplant survival rates were 85.7% for the HIV group (unchanged from 1 to 3 years) versus 82.2%, 81.2%, and 78.8% for the non-HIV group. Cumulative survival among HIV-HBV coinfected recipients was not significantly different from the HBV monoinfected recipients (log-rank test P = 0.692). The percentage of deaths attributed to infection was comparable between the HIV and non-HIV groups (14.3% vs. 9.32%, P = 0.665). Post OLT, there was no significant difference in acute rejection, cytomegalovirus infection, bacteremia, pulmonary infection, acute kidney injury, de novo tumor and vascular and biliary complications. CONCLUSIONS: Liver transplantation in patients with HIV-HBV coinfection yields excellent outcomes in terms of intermediate- or long-term survival rate and low incidence of postoperative complications in China. These findings suggest that OLT is safe and feasible for HIV-HBV coinfected patients with ESLD. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300067631), registered 11 January 2023.


Asunto(s)
Coinfección , Enfermedad Hepática en Estado Terminal , Infecciones por VIH , Hepatitis B , Trasplante de Hígado , Humanos , Enfermedad Hepática en Estado Terminal/cirugía , Hepatitis B/epidemiología , Virus de la Hepatitis B/genética , VIH , Infecciones por VIH/tratamiento farmacológico , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos
18.
J Int AIDS Soc ; 27(4): e26236, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38566482

RESUMEN

INTRODUCTION: In recent years, the expansion of HIV treatment eligibility has resulted in an increase in people with antiretroviral therapy (ART) experience prior to pregnancy but little is known about postpartum engagement in care in this population. We examined differences in disengagement from HIV care after delivery by maternal ART history before conception. METHODS: We analysed data from people living with HIV (aged 15-49) in Khayelitsha, South Africa, with ≥1 live birth between April 2013 and March 2019. We described trends over time in ART history prior to estimated conception, classifying ART history groups as: (A) on ART with no disengagement (>270 days with no evidence of HIV care); (B) returned before pregnancy following disengagement; (C) restarted ART in pregnancy after disengagement; and (D) ART new start in pregnancy. We used Kaplan-Meier curves and proportional-hazards models (adjusted for maternal age, number of pregnancy records and year of delivery) to examine the time to disengagement from delivery to 2 years postpartum. RESULTS: Among 7309 pregnancies (in 6680 individuals), the proportion on ART (A) increased from 19% in 2013 to 41% in 2019. The proportions of those who returned (B) and restarted (C) increased from 2% to 13% and from 2% to 10%, respectively. There was a corresponding decline in the proportion of new starts (D) from 77% in 2013 to 36% in 2019. In the first recorded pregnancy per person in the study period, 26% (95% CI 25-27%) had disengaged from care by 1 year and 34% (95% CI 33-36%) by 2 years postpartum. Individuals who returned (B: aHR 2.10, 95% CI 1.70-2.60), restarted (C: aHR 3.32, 95% CI 2.70-4.09) and newly started ART (D: aHR 2.41, 95% CI 2.12-2.74) had increased hazards of postpartum disengagement compared to those on ART (A). CONCLUSIONS: There is a growing population of people with ART experience prior to conception and postpartum disengagement varies substantially by ART history. Antenatal care presents an important opportunity to understand prior ART experiences and an entry into interventions for strengthened engagement in HIV care.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Embarazo , Humanos , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Estudios Retrospectivos , Sudáfrica/epidemiología , Periodo Posparto , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/epidemiología , Fármacos Anti-VIH/uso terapéutico
19.
BMC Public Health ; 24(1): 981, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589818

RESUMEN

BACKGROUND: Behavioral Diseases Counseling Centers (BDCCs) and Vulnerable Women's Counseling Centers (VWCCs) in Iran are the main peripheral centers that offer educational, counseling, diagnostic, preventive, curative and protective services to individuals living with or at high risk of contracting HIV/AIDS and female sex workers respectively. Due to the social stigma surrounding HIV in Iran, this study aims to identify the factors that may hinder or encourage HIV/AIDS patients and women with risky sexual behaviors from visiting these centers. METHODS: Conducted in 2023, this qualitative study involved individuals visiting BDCCs and VWCCs in two western provinces of Iran, Ilam and Kermanshah. The study participants included 21 health staff members working in BDCCs and VWCCs and 20 HIV/AIDS patients and vulnerable women with unsafe sexual behaviors referring to these centers. Purposive, snowball and maximum variation sampling techniques were applied to interview the participants. Interviews were conducted between January 5th and May 21st, 2023, using a semi-structure guideline. Interviews were transcribed and content analysis approach was applied to analyze data using MAXQDA20 software. RESULTS: According to the findings, the barriers and facilitators of visiting specialized centers for HIV/AIDS patients and vulnerable women were categorized into three main categories, 10 subcategories and 35 sub-subcategories including: Medical and operational processes (4 subcategories and 12 sub-subcategories), mutual interactions between the personnel and visitors (people living with and at the risk of getting HIV/AIDS) (3 subcategory and 13 sub-subcategories), and physical characteristics of the centers (3 subcategories and 10 sub-subcategories). CONCLUSIONS: To improve the performance of BDCCs and VWCCs and encourage people living with and at the risk of contracting HIV/AIDS to visit these centers regularly, health policy makers should consider modifying clinical processes, physical features, personnel behaviors and visitors' concerns raised by the interviewees and the issues identified in this study.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Trabajadores Sexuales , Humanos , Femenino , Síndrome de Inmunodeficiencia Adquirida/prevención & control , Infecciones por VIH/prevención & control , Infecciones por VIH/psicología , Utilización de Instalaciones y Servicios , Aceptación de la Atención de Salud , Investigación Cualitativa
20.
Health Res Policy Syst ; 22(1): 45, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589894

RESUMEN

INTRODUCTION: Globally, there are 37.7 million people living with human immunodeficiency virus (HIV). So far, there is no study done in Gambia which assessed comprehensive HIV knowledge and its associated factors. Therefore, this study aims to assess comprehensive HIV knowledge and its associated factors among reproductive-age women in Gambia. OBJECTIVE: To assess the prevalence of comprehensive HIV knowledge and its associated factors among reproductive-age women in Gambia. METHODS: The study used the Gambian Demographic and Health Survey, which was conducted from 21 November 2019 to 30 March 2020 in Gambia. The survey employed a stratified two-stage cluster sampling technique to recruit study participants. Logistic regression analysis was used to identify factors associated with HIV comprehensive knowledge. Statistical significance was declared at a P value of less than 0.05 with a 95% confidence interval (CI). RESULTS: The overall prevalence of comprehensive HIV knowledge was 27.1% (25.1-36.2%). Older age [adjusted odds ratio (AOR) of 1.20 (95% CI 1.16-1.26)], using contraceptive [AOR of 1.15 (95% CI 1.01-1.31)], higher education [AOR of 4.73 (95% CI 3.86-5.81)], rich wealth quintile [AOR of 1.61 (95% CI 1.37-1.87)], media exposure [AOR of 1.76 (95% CI 1.39-2.23)], ever tested for HIV [AOR of 1.55 (95% CI 1.42-1.74)], visited health facility within the last 12 months [AOR of 1.26 (95% CI 1.12-1.41)] and decision-making autonomy [AOR of 1.42 (95% CI 1.27-1.60)] were positively associated with comprehensive HIV knowledge. However, being married [AOR of 0.72 (95% CI 0.62-0.82)] was negatively associated with comprehensive HIV knowledge. CONCLUSIONS: The prevalence of comprehensive HIV knowledge was low in Gambia. Educational interventions that focused mainly on awareness creation about HIV/AIDS should be designed especially for married women and lower socio-economic status. An effort has to be made to address those disparities at the national level.


Asunto(s)
Infecciones por VIH , VIH , Humanos , Femenino , Gambia/epidemiología , Infecciones por VIH/epidemiología , Matrimonio , Encuestas y Cuestionarios
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